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Eur J Clin Invest. 2016 Feb;46(2):170-80. doi: 10.1111/eci.12581. Epub 2016 Jan 5.

Peripheral loss of CD8(+) CD161(++) TCRVα7·2(+) mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients.

Author information

1
Tropical Infectious Disease Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
2
Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
3
Department of Orthopaedic Surgery, Tissue Engineering Group (TEG), NOCERAL, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
4
Department of Microbiology and Immunology, Emory Vaccine Center, Atlanta, GA, USA.
5
Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
6
Centre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, Malaysia.

Abstract

BACKGROUND:

Mucosal-associated invariant T (MAIT) cells play an important role in innate host defence. MAIT cells appear to undergo exhaustion and are functionally weakened in chronic viral infections. However, their role in chronic hepatitis C virus (HCV) infection remains unclear.

MATERIALS AND METHODS:

We investigated the frequency of CD8(+) CD161(++) TCR Vα7.2(+) MAIT cells in a cross-sectional cohort of chronic HCV-infected patients (n = 25) and healthy controls (n = 25). Peripheral blood mononuclear cells were investigated for circulating MAIT cell frequency, liver-homing (CCR5 and CD103), biomarkers of immune exhaustion (PD-1, TIM-3 and CTLA-4), chronic immune activation (CD38 and HLA-DR), and immunosenescence (CD57) by flow cytometry.

RESULTS:

The frequency of MAIT cells was significantly decreased, and increased signs of immune exhaustion and chronic immune activation were clearly evident on MAIT cells of HCV-infected patients. Decrease of CCR5 on circulating MAIT cells is suggestive of their peripheral loss in chronic HCV-infected patients. MAIT cells also showed significantly increased levels of HLA-DR, CD38, PD-1, TIM-3 and CTLA-4, besides CD57 in chronic HCV disease.

CONCLUSIONS:

Immune exhaustion and senescence of CD8(+) CD161(++) TCR Vα7.2(+) MAIT cells could contribute to diminished innate defence attributes likely facilitating viral persistence and HCV disease progression.

KEYWORDS:

CD38; HCV infection; MAIT cells; PD-1; TCRVα7.2; exhaustion

PMID:
26681320
DOI:
10.1111/eci.12581
[Indexed for MEDLINE]

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